Distal myasthenia gravis with a decrement, an increment, and denervation.

We present two patients with distal myasthenia gravis poorly responsive to immunomodulatory therapy. In addition to a typical decrement on slow repetitive nerve stimulation, both had borderline to low compound muscle action potential (CMAP) amplitudes, a large increment in CMAP amplitude and area after exercise, and active denervation in distal muscles. Both had elevated acetylcholine receptor antibody (AChR Ab) levels, but normal voltage-gated calcium channel antibody levels.

Effects of PMP22 duplication and deletions on the axonal cytoskeleton.

Axonal loss in Charcot-Marie-Tooth type 1A (CMT1A) is an important feature correlated with the functional disability in affected individuals. It is not known, however, how the most common genetic defect in Schwann cells (PMP22 duplication) causes the CMT1A phenotype and results in axonal loss. In this study, sural nerve segments from individuals with PMP22 duplications or deletions, causing the reciprocal disorder hereditary neuropathy with pressure palsies (HNPP), were grafted into the cut ends of the sciatic nerve of nude mice.

A novel PMP22 point mutation causing HNPP phenotype: studies on nerve xenografts.

Background: Hereditary neuropathy with liability to pressure palsies (HNPP) in most cases is caused by a deletion in chromosome 17p11.2-12 or, rarely, mutations resulting in a functional loss of one copy of the peripheral myelin protein 22 (PMP22) gene. Point mutations that lie deep within transmembrane (TM) domains causing major structural changes in PMP22 are associated with severe neuropathy.

Abnormalities in the axonal cytoskeleton induced by a connexin32 mutation in nerve xenografts.

The X-linked form of Charcot-Marie-Tooth neuropathy is associated with mutations in the connexin32 (Cx32) gene. The functional role of Cx32 in Schwann cells and the relationship of these mutations to the progressive axonal loss and distal limb weakness seen in this disease have not been elucidated. To investigate the local influence of Schwann cells bearing the Cx32 gene defect on axonal cytoskeleton and the myelination process, the nerve xenograft model was used to transfer a Cx32 missense mutation (Glu102Gly) from human to an in vivo myelination system in nude mice.

Myotonic dystrophy with no trinucleotide repeat expansion.

We report 3 patients from 2 families with myotonic dystrophy who do not show an abnormal expansion of CTG trinucleotide repeats within the myotonic dystrophy gene. Characteristic features of myotonic dystrophy in these patients were frontal balding, cataracts, cardiac conduction abnormalities, and testicular atrophy with myotonia and muscle weakness. Results of muscle histopathology were consistent with myotonic dystrophy.

Andersen's syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features.

Andersen's syndrome is a clinically distinct form of potassium-sensitive periodic paralysis associated with cardiac dysrhythmias. The subtle nature of the cardiac and dysmorphic features may delay the recognition of this syndrome and its potentially lethal cardiac dysrhythmias. The genetic defect in Andersen's syndrome is not genetically linked to other forms of potassium-sensitive periodic paralysis and is probably distinct from the long QT syndrome locus.

Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders.

Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi.

Extreme variability of expression in monozygotic twins with FSH muscular dystrophy.

We describe monozygotic twins who are either discordant or show extreme variability in the expression of facioscapulohumeral muscular dystrophy (FSHD). One twin was severely incapacitated by FSHD. The asymptomatic twin demonstrated equivocal facial weakness on physical examination, but no difference on quantitative myometry when compared with normal controls.